title: Coronin-1A links cytoskeleton dynamics to TCR alpha beta-induced cell signaling.
abstract: Actin polymerization plays a critical role in activated T lymphocytes both in regulating T cell receptor (TCR)-induced immunological synapse (IS) formation and signaling. Using gene targeting, we demonstrate that the hematopoietic specific, actin- and Arp2/3 complex-binding protein coronin-1A contributes to both processes. Coronin-1A-deficient mice specifically showed alterations in terminal development and the survival of alpha beta T cells, together with defects in cell activation and cytokine production following TCR triggering. The mutant T cells further displayed excessive accumulation yet reduced dynamics of F-actin and the WASP-Arp2/3 machinery at the IS, correlating with extended cell-cell contact. Cell signaling was also affected with the basal activation of the stress kinases sAPK/JNK1/2; and deficits in TCR-induced Ca2+ influx and phosphorylation and degradation of the inhibitor of NF-kappaB (I kappa B). Coronin-1A therefore links cytoskeleton plasticity with the functioning of discrete TCR signaling components. This function may be required to adjust TCR responses to selecting ligands accounting in part for the homeostasis defect that impacts alpha beta T cells in coronin-1A deficient mice, with the exclusion of other lympho/hematopoietic lineages.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université Aix-Marseille, Marseille, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Mugnier
authors.forename: Béatrice
authors.initials: B
authors.lastname: Nal
authors.forename: Christophe
authors.initials: C
authors.lastname: Verthuy
authors.forename: Claude
authors.initials: C
authors.lastname: Boyer
authors.forename: David
authors.initials: D
authors.lastname: Lam
authors.forename: Lionel
authors.initials: L
authors.lastname: Chasson
authors.forename: Vincent
authors.initials: V
authors.lastname: Nieoullon
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chazal
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Guo
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: He
authors.forename: Dominique
authors.initials: D
authors.lastname: Rueff-Juy
authors.forename: Andrés
authors.initials: A
authors.lastname: Alcover
authors.forename: Pierre
authors.initials: P
authors.lastname: Ferrier
mesh_terms: D000199:Actins; D000818:Animals; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis; D003599:Cytoskeleton / Q000378:metabolism*; D006706:Homeostasis; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*
chemical_list: D000199:Actins; D016207:Cytokines; D008840:Microfilament Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C072061:coronin proteins